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Specialist Pharmacist in Clinical Nutrition
Great Ormond Street Hospital for Children NHS Trust
Broomfield Hospital Chelmsford, UK
Parenteral nutrition (PN) has been administered to infants and children with intestinal failure at Great Ormond Street Hospital for Children (GOSH) since the early 1970s.(1) The indications for PN are many and varied – it can be used for short periods of time when complete gut rest is required, or for longer periods in patients suffering from prolonged episodes of intestinal failure.
In 2001, 463 patients (4% of total inpatients) received PN for a total of 8,513 days (mean 18.38 days), and 50% (232) of patients were less than six months old when PN was commenced. Although 62% (288) of patients received PN for less than 14 days, 12% (60) received PN as inpatients for over a month (six of these were discharged on home parenteral nutrition).
Since the 1970s, the methods of compounding PN have changed and developed. Initially PN was administered directly to the patient from source containers of the nutrient solutions (glucose, amino acids and lipid) using a complex arrangement of lines joined by two- or three-way taps. Electrolytes were added to the glucose solution by medical or nursing staff on the ward before the start of infusion. Administering PN in this way was not without its complications – electrolyte incompatibilities were likely to occur, and the prevalence of line infections was high, often exceeding 20%.(2)
In an attempt to reduce the risk of infection it was recommended that PN solutions should be manufactured by qualified pharmacy staff within a dedicated aseptic preparation unit using a laminar flow hood.(3)
It is now standard practice in the UK for PN to be prepared in dedicated cleanroom facilities. In most of these units, one of two methods of manufacture are used:
Before February 2001, the two-stage process was used at GOSH to manufacture individually prescribed PN for over 20 patients a day. This process was time-consuming and it was becoming increasingly difficult to meet the demands for PN, which had increased by 25% since 1996. Consequently it was necessary to investigate alternative methods for manufacturing PN.
Automated compounding devices
Fully automated compounding devices (FACD) for the manufacture of PN have been widely used within the USA(4,5) and mainland Europe(6,7) for a number of years. The devices used include the Nutrimix (Abbott), MicroMacro 23 (Baxa) and Micromix (Clintec). These deliver fluid to the final container using either a volumetric or gravimetric fluid pumping system. The FACD is usually linked to dedicated software that electronically transfers information about PN formulations. A number of researchers have compared the accuracy of preparations of PN using FACD and manual methods,(8,9) and found that using a FACD for preparing PN solutions resulted in significant savings in personnel time, lessened costs and improved accuracy.
Validation of FACD
Before introducing a FACD (the Baxa MicroMacro 23 [MM23]), into the MCA (Medicines Control Agency) licensed pharmacy manufacturing unit at GOSH, it was necessary to perform extensive validation of the compounding equipment and operating systems. These validations were performed in accordance with the Good automated manufacturing practice guidelines,(10) and details given in the Rules and guidance to pharmaceutical manufacturers and distributors.(11) As part of the validation work, studies were performed comparing methods of compounding PN (the old two-stage method and the MM23). The results demonstrated no significant difference in terms of precision and accuracy between the two methods. However, PN solutions prepared using the MM23 had an increased number of particles present and did not fully meet the British Pharmacopoeia requirement for particles in the size range greater than 5.0mm.
The difference in the quantity and type of particles found in the PN solutions compounded by different methods may be due either to the plastic compounding apparatus used in the MM23, or to the lack of filtration of the electrolyte solutions in PN manufactured using this method. These results provide more evidence for the use of filters during the administration of PN to patients.(12,13)
Introduction of the MM23
The Baxa MM23 was introduced in February 2001 to manufacture the amino acid/glucose/electrolyte PN solutions. To ensure the smooth introduction of this compounding device, a number of training and operational issues were considered:
Daily operation of the MM23
The introduction of the MM23 has required significant changes in the routine within this busy pharmacy production unit.
The Baxa MicroMacro 23 has been used in this hospital to manufacture approximately 10,000 PN bags over the last year. The introduction of this fully automated compounding device has resulted in a significant improvement in the pharmacy-delivered PN service.
Fully automated compounding devices provide an accurate, fast and safe method of manufacturing PN within busy manufacturing units.
International Society for Pharmaceutical Engineering (ISPE) European Office
PO Box 18
T:+32 2 7434422
F:+32 2 7431550
For Validation of Automated Systems